Stem cell programming

Stem Cell programming
and reprogramming
Kayeen Vadakkan
Assistant Professor
Department of Biotechnology
St. Mary's College, Thrissur.

Stem cell programming
 Stem cell programming can be defined as the mechanism through
which a potent cell is programmed to an other functional cell.
This mechanism was first demonstrated by Davis et al in 1987, where
they converted murine fibroblast cells to cells with myogenic
properties.
Based on it’s mechanism stem cell programming can be classified
into two
Forward programming
Direct programming
Stem Cell Biology, Kayeen Vadakkan, St. Mary's College, Thrissur

Stem cell programming (Continues)
Stem cell programming is mediated by transcription factors which is
case specific (Transcription factors will change according to cell.
In programming of stem cell there will be minimum three
components.
Starting cell ( The cell that has to be converted)
Transcription Factors ( controls the programming)
Cell of choice (desired end product)

Stem cell programming (Continues)
Starting Cells
Cell of Choice
Transcription factors
Figure 1: Schematic representation of Stem cell programming

Types of Stem cell programming
 Based on mechanism and starting cell , Stem Cell programming can
be classified into two
Forward programming
Direct programming
 Through forward programming a non functional stem cell will be
converted to a functional cell.
 Through direct programming a functional cell will be converted to
another functional cell.

Forward programming of stem cells
 Forward programming materialize the conversion of pluripotent
stem cells into functional cell.
 It is noted that in forward programming, always the starting cell will
be a non-functional stem cell an end product will be a functional cell.
 In the process of forward programming there could be interference
of progenitor cell before formation of functional cell.

Forward programming of stem cells
(Continues)
Starting Cells
(Pluripotent cells)
Transcription factors Transcription factors
Intermediate
progenitor cells
Cell of Choice
(Functional cells)
Figure 2: Schematic representation of forward Stem cell programming

Direct programming of stem cells
Conversion of mature differentiated cells to another type of
functional cell is called direct programming.
In direct programming the starting cell will be differentiated cell
unlike pluripotent stem cell in forward programming.
It is also observed that direct stem cell programming does not
include any intermediate progenitor cell during the conversion.

Direct programming of stem cells
(Continues)
Starting Cells
(functional cell)
Cell of Choice
(Functional cell)
Figure 3 : Schematic representation of Direct Stem cell
programming

Programming of Human Pluripotent Stem cells
into Hematopoietic cells.
Human pluripotent stem cells provide best genomic landscape for
successful production of hematopoietic stem cells.
 For the conversion of HPS (human pluripotent stem cell) a number of
transcription factors are necessary.
Based on the involvement of transcription factors there are two methods
involved in the programming of Human Pluripotent Stem cells into
Hematopoietic cells.
• Single transcription factor mediated mechanism
• Multi transcription factor mediated mechanism

Single transcription factor mediated mechanism
In this type of programming there will be only a single transcription
factor involved.
The sole transcription factor involved in the programming of Human
Pluripotent Stem cells into Hematopoietic cells is TAL1 (T cell acute
lymphocytic leukemia 1).
TAL1 mediate the recognition of specific pluripotent stem cell,
development and differentiation into Hematopoietic cells.

Human Pluripotent Stem cells
( Starting cell)
Hematopoietic cells
(Cell of Choice)
TAL1
(Transcription factors)
Figure 4 : Schematic representation of Single transcription
factor mediated cell programming

Multi transcription factor mediated mechanism.
In this type of programming there will be several transcription factor involved
in the Programming of Human Pluripotent Stem cells into Hematopoietic cells.
The starting cell Human Pluripotent cells will be recognized by RUNx
transcription factor.
SOX17 will initiate the development of Human Pluripotent cells into
Hematopoietic cells and the differentiation mechanism will be regulated by
HOXa9.
The cumulative action of these three transcription factors will convert the
Human Pluripotent Stem cells into Hematopoietic cells.

Human Pluripotent Stem cells
( Starting cell)
RUN X1 ( recognition)
Figure 5 : Schematic representation of Multi transcription factor
mediated cell programming
Hematopoietic cells
(Cell of Choice)
SOX17 ( development)
HOX A9 (differentiation)

Reprogramming of cells.
 Stem cell reprogramming is defined as the mechanism through
which a fully differentiated stem cell is converted to un organized
pluripotent stage.
 There are three major techniques used for the reprogramming of
functional cell into pluripotent stage.
Somatic Cell Nuclear Transfer (SCNT)
Fusion of Cells
Induced pluripotent stem cells

Somatic Cell Nuclear Transfer (SCNT)
 In this method the nuclear from somatic cell will be transferred and
implanted in pluripotent cell.
Somatic Cell
Cell Nucleus
Pluripotent cell
Figure 6 : Schematic representation of Cell reprogramming by
Somatic Cell Nuclear Transfer (SCNT)

Reprogramming by Fusion of Cells
This is very primitive method of reprogramming by fusion of somatic
cell and pluripotent cells.
Somatic Cell
Pluripotent cell
Figure 7 : Schematic representation of Cell reprogramming by
Somatic Cell Fusion
Reprogrammed cell

Reprogramming by Induced pluripotency
In this method the cell reprograming is done by the induction of
pluripotency.
This reprograming is mediated by several transcription factors such as
NANG, KLF4, MYC
Somatic Cells
Induced Pluripotent cells

Stem cell programming

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