The document discusses hematopoiesis, the process of blood cell production. It covers the discovery of hematopoietic stem cells, their development and migration during embryogenesis, and their residence in the bone marrow in adults. It also details the cytokines and growth factors that control hematopoiesis, including early-acting and later-acting factors. Additionally, it examines cytokine receptors, signaling pathways, transcription factors, and the hematopoietic microenvironment including the stem cell niche in the bone marrow.

1. Presenter: Dr G Santhi priya
Moderator: Dr Rajeev

2. Contents
1. Introduction and development
2. Hematopoiesis
3. Cytokines and the Control of Hematopoiesis
4. Cytokine Receptors, Signaling Pathways, and Transcription Factors
5. Hematopoietic Microenvironment
6. References

3. • The pioneering work of Till and McCulloch began to
define the hierarchy of hematopoietic precursor cells
using in vivo clonal assays.
• Hematopoietic stem cells (HSCs) develop in discrete
anatomical niches, migrating during embryogenesis from
the aorta-gonadmesonephros (AGM) region to the fetal
liver, and finally to the bone marrow, where most HSCs
reside throughout adult life.
1. Introduction and development

5. 2. Hematopoiesis
•Defination :“The processes involved in the production of all of
the various cells of the blood from the HSCs are collectively
called hematopoiesis”
•Highly regulated process to maintain circulating cell numbers
within relatively constant levels and to respond rapidly to
conditions requiring extra cells .
•Maintains balance between self renewal, terminal differentiation,
migration, and cell death.

6. Sites of hematopoiesis

7. Hematopoietic cells

8. Stem Cells
• Multipotential precursors
• Stem Cell Phenotype:
CD34+Thy-1+CD49f +CD38-Lin-HLADR-Rh123Lo

10. The Stem Cell Compartment
“age hierarchy”
long-term repopulating cells (LTRs)
short-term repopulating cells (STRs)

11. Stem Cell Niches
• Ligand signaling pathway
• Growth factor receptor interactions

12. Progenitor Cells
•Populations of differentiating cells that have an increasingly limited capacity
to self-renew and are gradually more restricted in differentiation options.
•Lineage-specific transcription factors are thought to play essential roles in this
process

15. 3. Cytokines and the Control of Hematopoiesis
Growth factors / Cytokines

17. 3. Cytokines and the Control of Hematopoiesis
Growth factors / Cytokines
Early-Acting (Multilineage) Growth Factors Stem Cell Factor (SCF)
Flt3 Ligand (FL)
Interleukin 3
GM-CSF
Interleukin 6
Interleukin 11
Later-Acting (Lineage-Restricted) Growth G-CSF
Factors M-CSF
EPO
Indirect-Acting Growth Factors TPO
Other Stem Cell Regulators IL-5
IL-2,-4, -7, -10, -12, -13, -14, -15

18. 4. Cytokine Receptors, Signaling Pathways, and Transcription Factors
Cytokine Receptors: homodimers/ heterodimers or heterotrimers
Receptors with Intrinsic Tyrosine Kinase Domains
Hematopoietic Growth Factor Receptor Superfamily
Receptor Functional Domains

19. Signaling Pathways

21. Transcription Factors
•TFs associated with the activation of a particular lineage-specific
differentiation program often simultaneously inhibit alternate lineage-specific
transcription factors.
•Interestingly, more than half of the hematopoietic transcription factors
identified have been shown to be dysregulated in hematologic malignancies
(translocations, point mutations of TF genes)
•Thus, the impaired differentiation seen in leukemia is likely due to
abnormalities of critical, discrete pathways of transcriptional control.

22. Clinical Use of Hematopoietic Growth Factors

23. 5.Hematopoietic microenvironment

24. 5.Hematopoietic microenvironment

25. HSC niche players in the adult bone marrow

26. The aging HSC niche

27. • McKenzie SB, Williams JL. Hematopoiesis.In: Clinical labouratory
hematology, 3rd ed.Pearson;2016 p71-91.
•Singh T. Normal hematopoiesis and evaluation of bone marrow and
peripheral blood film. In: Atlas and Text of Haematology,3rd ed.Delhi:2014.P.1-
4
•Diseases of white blood cells, lymph nodes,spleen and thymus. In Kumar V,
Abbas A K, Aster J C, Robbins and cotran patholology basis of disease. 9th ed.
Elsevier Inc: 2016. P.579-82.
References

28. • Gao X, Xu C, Asada N, Frenette PS. The hematopoietic stem cell niche: from
embryo to adult. Development 2018;145:1-12
• Laffan M A, Manning R , Investigation of hemostasis, Bain B.J, Bates I, Laffan
M.A, Lewis S.M, Dacie and Lewis Practical Haematology. 11th ed. London:
2012. P.424-39
• Mathur SC,Hutchison RE,Mahi G. Hematopoiesis .In Bain B.J, Bates I, Laffan
M.A, Lewis S.M, Dacie and Lewis Practical Haematology. 11th ed. London:
2012. P.540-58
References

29. Thank you!!!