JAK-STAT signaling regulation of chicken embryonic stem cell differentiation into male germ cells

Yu Zhang1, Lei Zhang1, Qisheng Zuo1

  • 1Jiangsu Key Laboratory for Animal Genetic, Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, 88 South University Road, Yangzhou, Jiangsu, 225009, China.

Insights

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway promotes chicken germ cell formation. Activating JAK-STAT signaling increases primordial germ cells (PGCs), while inhibiting it decreases them.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Stem Cell Research

Background:

  • The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is vital for chicken germ stem cell differentiation.
  • The precise role of JAK-STAT signaling in regulating germ cell differentiation remained largely unknown prior to this study.

Purpose of the Study:

  • To investigate the role of JAK-STAT signaling in chicken germ cell differentiation.
  • To determine the effects of JAK-STAT pathway inhibition and activation on embryonic stem cells (ESCs) and primordial germ cells (PGCs) in vitro and in vivo.

Main Methods:

  • JAK-STAT signaling was modulated using cucurbitacin I (inhibition) or interleukin 6 (activation) during ESC differentiation.
  • Gene and protein expression of JAK-STAT pathway components (JAK2, STAT3) and PGC markers (CVH, C-KIT) were analyzed using Western blotting and qRT-PCR.
  • Histological analyses (PAS, immunohistochemistry) were performed on gonadal sections to assess PGC development and gonad size.

Main Results:

  • Inhibition of JAK-STAT signaling led to decreased JAK2 and STAT3 expression, reduced PGC markers, fewer CVH/C-KIT positive cells, and smaller gonads.
  • Activation of JAK-STAT signaling resulted in increased JAK2 and STAT3 expression, enhanced PGC marker CVH, a higher proportion of CVH/C-KIT positive cells, and significantly larger gonads.
  • JAK2 and STAT3 were identified as pivotal factors in JAK-STAT mediated intracellular signal transduction.

Conclusions:

  • JAK-STAT signaling effectively promotes PGC formation in the genital ridge during early embryogenesis in vivo.
  • The JAK-STAT pathway plays a positive regulatory role in the differentiation of ESCs to spermatogonial stem cells (SSCs) in vitro.
  • JAK2 and STAT3 are critical mediators of JAK-STAT signaling in germ cell development.

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